Altogether, 2374 participants from FTC were included for replication testing. These participants originated from the following cohorts: the Nicotine Addiction Genetics study of adult twins born in 1938–1957 and concordant for ever smoking, and their family members (mainly siblings); a population-based longitudinal study of five consecutive birth cohorts (1983–1987) of Finnish twins (FinnTwin12 sample); and a population-based longitudinal study of five consecutive birth cohorts (1975–1979) of Finnish twins (FinnTwin16 sample).36, 37, 38 Genotyping was done with the Illumina Human670-QuadCustom BeadChip (at the Wellcome Trust Sanger Institute) and the Illumina HumanCoreExome BeadChip (at the Wellcome Trust Sanger Institute and at the Broad Institute of MIT and Harvard). FTC samples were imputed with a large number of population samples, separately by genotyping array, with reference to 1000 Genomes (Phase I integrated variant set release [SHAPEIT2] in National Center for Biotechnology Information (NCBI) build 37 [hg19] coordinates) at the Institute for Molecular Medicine Finland. After imputation, FTC samples were merged together. Standardized residuals of the categorical FTND phenotype, regressed against SNP dosages, age, sex, birth cohort and the 10 first principal components (calculated